Synergistic Effect of Ginsenoside Rh2 Combines with Ionizing Radiation on CT26/<i>luc</i> Colon Carcinoma Cells and Tumor-Bearing Animal Model

Background: The local tumor control rate of colon cancer by radiotherapy is unsatisfactory due to recurrence and radioresistance. Ginsenoside Rh2 (Rh2), a panoxadiol saponin, possesses various antitumor effects. Methods: CT26/<i>luc</i> murine colon carcinoma cells and a CT26/<i>lu...

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Main Authors: Shan-Chih Lee, Chao-Yu Shen, Wei-Hsun Wang, Yen-Po Lee, Keng-Wei Liang, Ying-Hsiang Chou, Yeu-Sheng Tyan, Jeng-Jong Hwang
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/16/9/1188
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author Shan-Chih Lee
Chao-Yu Shen
Wei-Hsun Wang
Yen-Po Lee
Keng-Wei Liang
Ying-Hsiang Chou
Yeu-Sheng Tyan
Jeng-Jong Hwang
author_facet Shan-Chih Lee
Chao-Yu Shen
Wei-Hsun Wang
Yen-Po Lee
Keng-Wei Liang
Ying-Hsiang Chou
Yeu-Sheng Tyan
Jeng-Jong Hwang
author_sort Shan-Chih Lee
collection DOAJ
description Background: The local tumor control rate of colon cancer by radiotherapy is unsatisfactory due to recurrence and radioresistance. Ginsenoside Rh2 (Rh2), a panoxadiol saponin, possesses various antitumor effects. Methods: CT26/<i>luc</i> murine colon carcinoma cells and a CT26/<i>luc</i> tumor-bearing animal model were used to investigate the therapeutic efficacy of Rh2 combined with ionizing radiation and the underlying mechanisms. Results: Rh2 caused cell cycle arrest at the G1 phase in CT26/<i>luc</i> cells; however, when combined with ionizing radiation, the cells were arrested at the G2/M phase. Rh2 was found to suppress the activity of NF-κB induced by radiation by inhibiting the MAPK pathway, consequently affecting the expression of effector proteins. In an in vivo study, the combination treatment significantly increased tumor growth delay time and overall survival. Furthermore, the combination treatment significantly reduced NF-κB and NF-κB-related effector proteins, along with PD-1 receptor expression. Additionally, Rh2 administration led to increased levels of interleukin-12, -18, and interferon-γ in the mice’s sera. Importantly, biochemical analysis revealed no toxicities associated with Rh2 alone or combined with radiation. Conclusions: The combination of Rh2 with radiation may have potential as an alternative to improve the therapeutic efficacy of colorectal cancer.
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spelling doaj.art-4615b9ce69cd484faf254fedba7ba25f2023-11-19T12:23:44ZengMDPI AGPharmaceuticals1424-82472023-08-01169118810.3390/ph16091188Synergistic Effect of Ginsenoside Rh2 Combines with Ionizing Radiation on CT26/<i>luc</i> Colon Carcinoma Cells and Tumor-Bearing Animal ModelShan-Chih Lee0Chao-Yu Shen1Wei-Hsun Wang2Yen-Po Lee3Keng-Wei Liang4Ying-Hsiang Chou5Yeu-Sheng Tyan6Jeng-Jong Hwang7Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung 40201, TaiwanDepartment of Medical Imaging, Chung Shan Medical University Hospital, School of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanDepartment of Orthopedic Surgery, Changhua Christian Hospital, Changhua 50044, TaiwanDepartment of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei Branch, Hsinchu City 30010, TaiwanDepartment of Medical Imaging, Chung Shan Medical University Hospital, School of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanDepartment of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung 40201, TaiwanDepartment of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung 40201, TaiwanDepartment of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung 40201, TaiwanBackground: The local tumor control rate of colon cancer by radiotherapy is unsatisfactory due to recurrence and radioresistance. Ginsenoside Rh2 (Rh2), a panoxadiol saponin, possesses various antitumor effects. Methods: CT26/<i>luc</i> murine colon carcinoma cells and a CT26/<i>luc</i> tumor-bearing animal model were used to investigate the therapeutic efficacy of Rh2 combined with ionizing radiation and the underlying mechanisms. Results: Rh2 caused cell cycle arrest at the G1 phase in CT26/<i>luc</i> cells; however, when combined with ionizing radiation, the cells were arrested at the G2/M phase. Rh2 was found to suppress the activity of NF-κB induced by radiation by inhibiting the MAPK pathway, consequently affecting the expression of effector proteins. In an in vivo study, the combination treatment significantly increased tumor growth delay time and overall survival. Furthermore, the combination treatment significantly reduced NF-κB and NF-κB-related effector proteins, along with PD-1 receptor expression. Additionally, Rh2 administration led to increased levels of interleukin-12, -18, and interferon-γ in the mice’s sera. Importantly, biochemical analysis revealed no toxicities associated with Rh2 alone or combined with radiation. Conclusions: The combination of Rh2 with radiation may have potential as an alternative to improve the therapeutic efficacy of colorectal cancer.https://www.mdpi.com/1424-8247/16/9/1188colorectal cancerginsenoside Rh2radiotherapyimmunomodulation
spellingShingle Shan-Chih Lee
Chao-Yu Shen
Wei-Hsun Wang
Yen-Po Lee
Keng-Wei Liang
Ying-Hsiang Chou
Yeu-Sheng Tyan
Jeng-Jong Hwang
Synergistic Effect of Ginsenoside Rh2 Combines with Ionizing Radiation on CT26/<i>luc</i> Colon Carcinoma Cells and Tumor-Bearing Animal Model
Pharmaceuticals
colorectal cancer
ginsenoside Rh2
radiotherapy
immunomodulation
title Synergistic Effect of Ginsenoside Rh2 Combines with Ionizing Radiation on CT26/<i>luc</i> Colon Carcinoma Cells and Tumor-Bearing Animal Model
title_full Synergistic Effect of Ginsenoside Rh2 Combines with Ionizing Radiation on CT26/<i>luc</i> Colon Carcinoma Cells and Tumor-Bearing Animal Model
title_fullStr Synergistic Effect of Ginsenoside Rh2 Combines with Ionizing Radiation on CT26/<i>luc</i> Colon Carcinoma Cells and Tumor-Bearing Animal Model
title_full_unstemmed Synergistic Effect of Ginsenoside Rh2 Combines with Ionizing Radiation on CT26/<i>luc</i> Colon Carcinoma Cells and Tumor-Bearing Animal Model
title_short Synergistic Effect of Ginsenoside Rh2 Combines with Ionizing Radiation on CT26/<i>luc</i> Colon Carcinoma Cells and Tumor-Bearing Animal Model
title_sort synergistic effect of ginsenoside rh2 combines with ionizing radiation on ct26 i luc i colon carcinoma cells and tumor bearing animal model
topic colorectal cancer
ginsenoside Rh2
radiotherapy
immunomodulation
url https://www.mdpi.com/1424-8247/16/9/1188
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